Erythromycin inhibits wear debris‐induced inflammatory osteolysis in a murine model

• DOI: 10.1002/jor.20004
• Publication Date: 2005-10-27T21:17:51Z
• Authors: Weiping Ren; Bin Wu; Xin Peng; Lois Mayton; Dongzi Yu; JuanJie Ren; Ben D. Chen; Paul H. Wooley
• Keywords: Osteolysis; Calvaria; Histology

Abstract Up to 20% of patients with total joint arthroplasty will develop radiographic evidence aseptic loosening (AL), which most likely results from an inflammatory response billions wear debris shed the implant. Our previous work has demonstrated that erythromycin (EM), a macrolide antibiotic, inhibits debris‐induced osteoclastogenesis through reduction cytokine production and osteoclast differentiation, both involve NF‐κB pathway. The aim current study was determine whether EM osteolysis in murine model. Ultrahigh molecular‐weight polyethylene (UHMWPE) introduced into established air pouches on BALB/c mice, followed by implantation calvaria bone syngeneic littermates. (2 mg/kg/day) given mice intraperitoneally 2 days before UHMWPE introduction maintained until sacrifice mice. Mice without treatment, as well control injected saline alone were included this study. Pouch tissues collected 14 after inoculation for molecular histology analysis. findings indicate that: (1) reduced UHMWPE‐induced tissue inflammation, including diminished pouch membrane thickness, cellular infiltration, lowered IL‐1β TNF‐α expression (mRNA protein); (2) inhibited osteoclastogenesis, gene activation RANK, RANKL, CPK, RANKL stimulated pouches, (3) markedly number TRAP + cells tissues, protected against collagen depletion. In conclusion, provides particles‐induced model, represents promising therapeutic candidate prevention treatment AL. © 2005 Orthopaedic Research Society. Published Wiley Periodicals, Inc. J Orthop Res